This proposal of support for an eight bed General Clinical Research Center, its associated Core Laboratory and Outpatient Research Center in large medical center for children affiliated with Harvard Medical School. Children's Hospital has 325, with approximately 18,00 inpatient admissions and 300,000 outpatient visits annually. Our major goal in clinical investigation coincides with our mission to improve the health and welfare of children, which was exemplified when the 1996 Award for Excellence in Clinical Research was bestowed upon David. G. Nathan, our former Principal Investigator. Our central mission to apply basic biology to clinical problems as they affect children, by using this knowledge to elucidate mechanisms of disease which lead to the formation of novel therapies. During the past five year term of our GCRC grant, we have begun to see advances in research on angiogenesis translated into novel therapies for vascular and neoplastic disorders. Our investigators have defined the molecular basis for several immunodeficiency diseases of childhood, as well, as well as neurologic and neuromuscular disorders such as Angelman syndrome. We have used the knowledge that clotrimazole modulates ion channels to devise a potentially effective therapy for sickle cell disease. We continue to evaluate the best means for cardiopulmonary bypass for children undergoing surgery for congenital cardiac defects, and have made progress in our understanding of preterm labor. We have used animal models of graft versus host disease ti implement human trials of cytokine antagonists. During the past five years, the number of protocols supported by the Center has more than doubled, and a major goal of the next five years is to continue to stimulate the resurgence of clinical research within our institution, and to facilitate the links between our basic scientists and clinical investigators, such as via protocols which utilize the Harvard Gene Therapy Initiative. We believe that our Center represents the most important mission of Children's Hospital and makes excellent use of its outstanding resources and environment.